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Search Results: 1 - 10 of 464416 matches for " Kelly A Brayton "
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Carriage of stx2a Differentiates Clinical and Bovine-Biased Strains of Escherichia coli O157
Smriti Shringi, Carrie Schmidt, Kaya Katherine, Kelly A. Brayton, Dale D. Hancock, Thomas E. Besser
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051572
Abstract: Background Shiga toxin (Stx) are cardinal virulence factors of enterohemorrhagic E. coli O157:H7 (EHEC O157). The gene content and genomic insertion sites of Stx-associated bacteriophages differentiate clinical genotypes of EHEC O157 (CG, typical of clinical isolates) from bovine-biased genotypes (BBG, rarely identified among clinical isolates). This project was designed to identify bacteriophage-mediated differences that may affect the virulence of CG and BBG. Methods Stx-associated bacteriophage differences were identified by whole genome optical scans and characterized among >400 EHEC O157 clinical and cattle isolates by PCR. Results Optical restriction maps of BBG strains consistently differed from those of CG strains only in the chromosomal insertion sites of Stx2-associated bacteriophages. Multiplex PCRs (stx1, stx2a, and stx2c as well as Stx-associated bacteriophage - chromosomal insertion site junctions) revealed four CG and three BBG that accounted for >90% of isolates. All BBG contained stx2c and Stx2c-associated bacteriophage – sbcB junctions. All CG contained stx2a and Stx2a-associated bacteriophage junctions in wrbA or argW. Conclusions Presence or absence of stx2a (or another product encoded by the Stx2a-associated bacteriophage) is a parsimonious explanation for differential virulence of BBG and CG, as reflected in the distributions of these genotypes in humans and in the cattle reservoir.
Identification of Anaplasma marginale Type IV Secretion System Effector Proteins
Svetlana Lockwood, Daniel E. Voth, Kelly A. Brayton, Paul A. Beare, Wendy C. Brown, Robert A. Heinzen, Shira L. Broschat
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027724
Abstract: Background Anaplasma marginale, an obligate intracellular alphaproteobacterium in the order Rickettsiales, is a tick-borne pathogen and the leading cause of anaplasmosis in cattle worldwide. Complete genome sequencing of A. marginale revealed that it has a type IV secretion system (T4SS). The T4SS is one of seven known types of secretion systems utilized by bacteria, with the type III and IV secretion systems particularly prevalent among pathogenic Gram-negative bacteria. The T4SS is predicted to play an important role in the invasion and pathogenesis of A. marginale by translocating effector proteins across its membrane into eukaryotic target cells. However, T4SS effector proteins have not been identified and tested in the laboratory until now. Results By combining computational methods with phylogenetic analysis and sequence identity searches, we identified a subset of potential T4SS effectors in A. marginale strain St. Maries and chose six for laboratory testing. Four (AM185, AM470, AM705 [AnkA], and AM1141) of these six proteins were translocated in a T4SS-dependent manner using Legionella pneumophila as a reporter system. Conclusions The algorithm employed to find T4SS effector proteins in A. marginale identified four such proteins that were verified by laboratory testing. L. pneumophila was shown to work as a model system for A. marginale and thus can be used as a screening tool for A. marginale effector proteins. The first T4SS effector proteins for A. marginale have been identified in this work.
Identification of Rhipicephalus microplus Genes That Modulate the Infection Rate of the Rickettsia Anaplasma marginale
Ricardo F. Mercado-Curiel, María L. ávila-Ramírez, Guy H. Palmer, Kelly A. Brayton
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091062
Abstract: Arthropod vectors transmit a diversity of animal and human pathogens, ranging from RNA viruses to protozoal parasites. Chemotherapeutic control of pathogens has classically focused either on insecticides that kill the vector itself or antimicrobials for infected patients. The limitation of the former is that it targets both infected and uninfected vectors and selects for resistant populations while the latter requires prompt and accurate diagnosis. An alternative strategy is to target vector molecules that permit the pathogen to establish itself, replicate, and/or develop within the vector. Using the rickettsial pathogen Anaplasma marginale and its tropical tick vector, Rhipicephalus microplus, as a model, we tested whether silencing specific gene targets would affect tick infection rates (the % of fed ticks that are infected with the pathogen) and pathogen levels within infected ticks. Silencing of three R. microplus genes, CK187220, CV437619 and TC18492, significantly decreased the A. marginale infection rate in salivary glands, whereas gene silencing of TC22382, TC17129 and TC16059 significantly increased the infection rate in salivary glands. However in all cases of significant difference in the infection rate, the pathogen levels in the ticks that did become infected, were not significantly different. These results are consistent with the targeted genes affecting the pathogen at early steps in infection of the vector rather than in replication efficiency. Identifying vector genes and subsequent determination of the encoded functions are initial steps in discovery of new targets for inhibiting pathogen development and subsequent transmission.
Expression Patterns of Anaplasma marginale msp2 Variants Change in Response to Growth in Cattle, and Tick Cells versus Mammalian Cells
Adela S. Oliva Chávez, Roderick F. Felsheim, Timothy J. Kurtti, Pei-Shin Ku, Kelly A. Brayton, Ulrike G. Munderloh
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036012
Abstract: Antigenic variation of major surface proteins is considered an immune-evasive maneuver used by pathogens as divergent as bacteria and protozoa. Likewise, major surface protein 2 (Msp2) of the tick-borne pathogen, Anaplasma marginale, is thought to be involved in antigenic variation to evade the mammalian host immune response. However, this dynamic process also works in the tick vector in the absence of immune selection pressure. We examined Msp2 variants expressed during infection of four tick and two mammalian cell-lines to determine if the presence of certain variants correlated with specific host cell types. Anaplasma marginale colonies differed in their development and appearance in each of the cell lines (P<0.001). Using Western blots probed with two Msp2-monospecific and one Msp2-monoclonal antibodies, we detected expression of variants with differences in molecular weight. Immunofluorescence-assay revealed that specific antibodies bound from 25 to 60% of colonies, depending on the host cell-line (P<0.001). Molecular analysis of cloned variant-encoding genes demonstrated expression of different predominant variants in tick (V1) and mammalian (V2) cell-lines. Analysis of the putative secondary structure of the variants revealed a change in structure when A. marginale was transferred from one cell-type to another, suggesting that the expression of particular Msp2 variants depended on the cell-type (tick or mammalian) in which A. marginale developed. Similarly, analysis of the putative secondary structure of over 200 Msp2 variants from ticks, blood samples, and other mammalian cells available in GenBank showed the predominance of a specific structure during infection of a host type (tick versus blood sample), demonstrating that selection of a possible structure also occurred in vivo. The selection of a specific structure in surface proteins may indicate that Msp2 fulfils an important role in infection and adaptation to diverse host systems. Supplemental in Spanish (File S1) is provided.
Conservation in the face of diversity: multistrain analysis of an intracellular bacterium
Michael J Dark, David R Herndon, Lowell S Kappmeyer, Mikel P Gonzales, Elizabeth Nordeen, Guy H Palmer, Donald P Knowles, Kelly A Brayton
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-16
Abstract: These comparisons revealed that A. marginale has a closed-core genome with few highly plastic regions, which include the msp2 and msp3 genes, as well as the aaap locus. Comparison of the Florida and St. Maries genome sequences found that SNPs comprise 0.8% of the longer Florida genome, with 33.5% of the total SNPs between all five strains present in at least two strains and 3.0% of SNPs present in all strains except Florida. Comparison of genomes from three strains of Mycobacterium tuberculosis, Bacillus anthracis, and Nessieria meningiditis, as well as four Chlamydophila pneumoniae strains found that 98.8%–100% of SNPs are unique to each strain, suggesting A. marginale, with 76.0%, has an intermediate level of strain-specific SNPs. Comparison of genomes from other organisms revealed variation in diversity that did not segregate with the environmental niche the bacterium occupies, ranging from 0.00% to 8.00% of the larger pairwise-compared genome.Analysis of multiple A. marginale strains suggests intracellular bacteria have more variable SNP retention rates than previously reported, and may have closed-core genomes in response to the host organism environment and/or reductive evolution.While the recent boom in genome sequencing projects has provided a wealth of information about bacterial metabolism and evolution, we know little about interstrain variation. A firm understanding of the rates and sites of variation is useful in determining genotypic differences associated with phenotypic traits and in formulating control strategies for a number of pathogens. Further, knowledge about the pan-genome of organisms will aid in determining the core genomic requirements, as well as shed more light on events that occur in the various environmental niches bacteria occupy.Most studies of bacterial diversity to date have either utilized specific genomic loci [1,2] or have examined metagenomics of specific environmental niches [3,4]. While these types of studies help elucidate th
Genetic Diversity of Tick-Borne Rickettsial Pathogens; Insights Gained from Distant Strains
Sebastián Aguilar Pierlé,Ivan Imaz-Rosshandler,Ammielle Akim Kerudin,Jacqueline Sambono,Ala Lew-Tabor,Peter Rolls,Claudia Rangel-Escare?o,Kelly A. Brayton
Pathogens , 2014, DOI: 10.3390/pathogens3010057
Abstract: The ability to capture genetic variation with unprecedented resolution improves our understanding of bacterial populations and their ability to cause disease. The goal of the pathogenomics era is to define genetic diversity that results in disease. Despite the economic losses caused by vector-borne bacteria in the Order Rickettsiales, little is known about the genetic variants responsible for observed phenotypes. The tick-transmitted rickettsial pathogen Anaplasma marginale infects cattle in tropical and subtropical regions worldwide, including Australia. Genomic analysis of North American A. marginale strains reveals a closed core genome defined by high levels of Single Nucleotide Polymorphisms (SNPs). Here we report the first genome sequences and comparative analysis for Australian strains that differ in virulence and transmissibility. A list of genetic differences that segregate with phenotype was evaluated for the ability to distinguish the attenuated strain from virulent field strains. Phylogenetic analyses of the Australian strains revealed a marked evolutionary distance from all previously sequenced strains. SNP analysis showed a strikingly reduced genetic diversity between these strains, with the smallest number of SNPs detected between any two A. marginale strains. The low diversity between these phenotypically distinct bacteria presents a unique opportunity to identify the genetic determinants of virulence and transmission.
Genome Sequence of Babesia bovis and Comparative Analysis of Apicomplexan Hemoprotozoa
Kelly A Brayton ,Audrey O. T Lau,David R Herndon,Linda Hannick,Lowell S Kappmeyer,Shawn J Berens,Shelby L Bidwell,Wendy C Brown,Jonathan Crabtree,Doug Fadrosh,Tamara Feldblum,Heather A Forberger,Brian J Haas,Jeanne M Howell,Hoda Khouri,Hean Koo,David J Mann,Junzo Norimine,Ian T Paulsen,Diana Radune,Qinghu Ren,Roger K Smith Jr.,Carlos E Suarez,Owen White,Jennifer R Wortman,Donald P Knowles Jr.,Terry F McElwain ,Vishvanath M Nene
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030148
Abstract: Babesia bovis is an apicomplexan tick-transmitted pathogen of cattle imposing a global risk and severe constraints to livestock health and economic development. The complete genome sequence was undertaken to facilitate vaccine antigen discovery, and to allow for comparative analysis with the related apicomplexan hemoprotozoa Theileria parva and Plasmodium falciparum. At 8.2 Mbp, the B. bovis genome is similar in size to that of Theileria spp. Structural features of the B. bovis and T. parva genomes are remarkably similar, and extensive synteny is present despite several chromosomal rearrangements. In contrast, B. bovis and P. falciparum, which have similar clinical and pathological features, have major differences in genome size, chromosome number, and gene complement. Chromosomal synteny with P. falciparum is limited to microregions. The B. bovis genome sequence has allowed wide scale analyses of the polymorphic variant erythrocyte surface antigen protein (ves1 gene) family that, similar to the P. falciparum var genes, is postulated to play a role in cytoadhesion, sequestration, and immune evasion. The ~150 ves1 genes are found in clusters that are distributed throughout each chromosome, with an increased concentration adjacent to a physical gap on chromosome 1 that contains multiple ves1-like sequences. ves1 clusters are frequently linked to a novel family of variant genes termed smorfs that may themselves contribute to immune evasion, may play a role in variant erythrocyte surface antigen protein biology, or both. Initial expression analysis of ves1 and smorf genes indicates coincident transcription of multiple variants. B. bovis displays a limited metabolic potential, with numerous missing pathways, including two pathways previously described for the P. falciparum apicoplast. This reduced metabolic potential is reflected in the B. bovis apicoplast, which appears to have fewer nuclear genes targeted to it than other apicoplast containing organisms. Finally, comparative analyses have identified several novel vaccine candidates including a positional homolog of p67 and SPAG-1, Theileria sporozoite antigens targeted for vaccine development. The genome sequence provides a greater understanding of B. bovis metabolism and potential avenues for drug therapies and vaccine development.
Working Stiff(s) on Reality Television during the Great Recession
Sean Brayton
Societies , 2012, DOI: 10.3390/soc2040235
Abstract: This essay traces some of the narratives and cultural politics of work on reality television after the economic crash of 2008. Specifically, it discusses the emergence of paid labor shows like Ax Men, Black Gold and Coal and a resurgent interest in working bodies at a time when the working class in the US seems all but consigned to the dustbin of history. As an implicit response to the crisis of masculinity during the Great Recession these programs present an imagined revival of manliness through the valorization of muscle work, which can be read in dialectical ways that pivot around the white male body in peril. In Ax Men, Black Gold and Coal, we find not only the return of labor but, moreover, the re-embodiment of value as loggers, roughnecks and miners risk both life and limb to reach company quotas. Paid labor shows, in other words, present a complicated popular pedagogy of late capitalism and the body, one that relies on anachronistic narratives of white masculinity in the workplace to provide an acute critique of expendability of the body and the hardships of physical labor.
Filtering the fiber of the pinch map
Brayton Gray
Mathematics , 2008, DOI: 10.2140/gtm.2008.13.203
Abstract: A new type of Hopf invariant is described for the fiber of the pinch map from the mapping cone of a map from A to X onto to the suspension of A; this is then used to study the boundary map in the fibration sequence of Cohen, Moore and Neisendorfer in the case that the mapping cone is an odd dimensional Moore space. The components of the boundary map are then shown to be compatible with Hopf invariants and a filtered splitting of the loops on the fiber is obtained.
Decompositions involving Anick's spaces
Brayton Gray
Mathematics , 2008,
Abstract: Recently Stephen Theriault and I found an elementary construction of Anick's spaces and proved their main properties(arXiv:0710.1024).In this work the fundamental fibration is decomposed. This is useful in studying maps out of Anick's spaces and will be needed in order to determine it's universal properties.
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